Inhaled Medicines
Optimizing Development through Integration of In Silico, In Vitro and In Vivo Approaches
- 1st Edition - January 20, 2021
- Editors: Stavros Kassinos, Per Bäckman, Joy Conway, Anthony J. J. Hickey
- Language: English
- Paperback ISBN:9 7 8 - 0 - 1 2 - 8 1 4 9 7 4 - 4
- eBook ISBN:9 7 8 - 0 - 1 2 - 8 1 4 9 7 5 - 1
Inhaled medicines are widely used to treat pulmonary and systemic diseases. The efficacy and safety of these medicines can be influenced by the deposited fraction, the regional de… Read more
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Request a sales quoteInhaled medicines are widely used to treat pulmonary and systemic diseases. The efficacy and safety of these medicines can be influenced by the deposited fraction, the regional deposition pattern within the lungs and by post-depositional events such as drug dissolution, absorption and clearance from the lungs. Optimizing performance of treatments thus requires that we understand and are able to quantify these product and drug attributes.
Inhaled Medicines: Optimizing Development through Integration of In Silico, In Vitro and In Vivo Approaches
explores the current state of the art with respect to inhalation drug delivery, technologies available to assess product performance, and novel in silico methods now available to link in vitro product performance to clinical performance. Recent developments in the latter field, especially the prospect of integration of three-dimensional Computational Fluid Particle Methods (3D-CFPD) with physiologically based pharmacokinetic (PBPK models), unlocks the potential for in silico population studies that can help inform and optimize treatment and product development strategies. In this highly multidisciplinary field, where progress occurs at the intersection of several disciplines of engineering and science, this work aims to integrate current knowledge and understanding and to articulate a clear vision for future developments.- Considers the healthcare needs driving the field, and where inhaled drugs could have the maximum impact
- Gives a concise account of the state of the art in key areas and technologies such as device and formulation technologies, clinically relevant in vitro performance assessment, medical imaging, as well as in silico modelling and simulation
- Articulates how the combination of in vitro product performance data, medical imaging and simulations technologies in the framework of large scale in silico pre-clinical trials could revolutionize the field
- Provides systematic and thorough referencing to sources offering a more-in-depth analysis of technical issues
Pharmaceutical scientists and engineers working on inhalation products: including researchers in basic research and development, academic researchers, industrial researchers, doctoral researchers, and senior researchers; Regulators, policy makers, and funding agencies who require an overview of the potential of the technologies involved with inhaled medicines
- Cover image
- Title page
- Table of Contents
- Copyright
- List of contributors
- Introduction
- Chapter 1. Historical perspective – Disruptive technologies and strategies
- Abstract
- 1.1 Dosage forms
- 1.2 Characterization
- 1.3 Biopharmaceutics
- 1.4 Conclusion
- References
- Chapter 2. The API
- Abstract
- 2.1 Introduction
- 2.2 Considerations for designing inhaled molecules
- 2.3 Physicochemical properties of pulmonary drugs
- 2.4 Drivers for pulmonary absorption and retention
- References
- Chapter 3. Devices and formulations: General introduction and wet aerosol delivery systems
- Abstract
- 3.1 General introduction
- 3.2 Wet aerosol delivery systems
- 3.3 Breath control and breath adapted aerosol delivery (AAD)
- 3.4 Drug formulations for wet aerosol generation
- 3.5 The performance of nebulizers
- 3.6 Discussion and future perspectives
- References
- Chapter 4. Metered dose inhalers (MDIs)
- Abstract
- 4.1 Introduction
- 4.2 Basic MDI design, manufacturing and working principle
- 4.3 Drug formulations for MDIs
- 4.4 Special MDI types and add-on devices for MDIs
- 4.5 The performance of MDIs
- 4.6 Discussion and future perspectives
- References
- Chapter 5. Dry powder inhalers (DPIs)
- Abstract
- 5.1 Introduction
- 5.2 DPI design: general description and considerations
- 5.3 Aerosol particle manufacturing techniques for DPIs
- 5.4 Powder formulations for DPIs
- 5.5 The dry powder inhaler device
- 5.6 DPI performance
- 5.7 Discussion and future perspectives
- 5.8 In silico simulation of pulmonary delivery systems
- References
- Chapter 6. In vitro methods to study dose deposition
- Abstract
- 6.1 Introduction
- 6.2 The lung dose
- 6.3 Realistic in vitro testing
- 6.4 Realistic estimation of the (initial) total lung dose
- 6.5 Realistic estimation of the regional lung dose
- 6.6 Data usage
- References
- Chapter 7. In silico methods to model dose deposition
- Abstract
- 7.1 Introduction
- 7.2 The different roles of in silico methods
- 7.3 Choosing the appropriate in silico method based on lung region and underlying objective
- 7.4 3D CFPD in the extrathoracic and conducting airways
- 7.5 Modeling deposition in the acinus
- 7.6 Towards integrated simulations covering the whole lung and combining more than one type of modeling
- 7.7 Simulations for the non-standard lung: Accounting for the effects of sex disease and age
- 7.8 1D and reduced models
- 7.9 Conclusions
- References
- Chapter 8. Non-absorptive clearance from airways
- Abstract
- 8.1 Introduction
- 8.2 Lung anatomy and physiology
- 8.3 Measuring clearance in humans
- 8.4 Measuring clearance in animals
- 8.5 Modeling airway clearance
- 8.6 Future developments
- 8.7 Conclusions
- References
- Chapter 9. Dissolution and drug release
- Abstract
- 9.1 Introduction
- 9.2 Elemental concepts in dissolution process
- 9.3 Dissolution of orally inhaled drug products (OIDPs)
- 9.4 Mathematical description and statistical assessment of dissolution profiles
- 9.5 Conclusion and regulatory considerations
- References
- Appendix 9.A1 Schematic configuration of compendial particle sizing apparatuses
- Chapter 10. Epithelial permeability and drug absorption in the lungs
- Abstract
- 10.1 Absorptive clearance from the lungs
- 10.2 Epithelial drug transport
- 10.3 Lung retention
- 10.4 Experimental models for lung permeability
- 10.5 Measures of absorptive transport
- 10.6 Mathematical modeling of pulmonary absorption
- 10.7 Conclusion
- References
- Chapter 11. Drug distribution in lung tissue
- Abstract
- 11.1 Introduction
- 11.2 Pharmacokinetic concepts of drug distribution in tissue
- 11.3 Mechanisms of pulmonary drug distribution
- 11.4 Spatial distribution of compounds in lung tissue
- 11.5 Summary
- 11.6 Outlook
- References
- Chapter 12. Physiologically-based pharmacokinetic modeling after drug inhalation
- Abstract
- 12.1 Introduction
- 12.2 Features of empirical and mechanistic pharmacometric approaches
- 12.3 Published PBPK models for orally inhaled drugs
- 12.4 Future applications of PBPK modeling for inhaled drugs - opportunities and limitations
- 12.5 Conclusions and outline
- Acknowledgments
- References
- Chapter 13. Inhaled aerosols: Emerging clinical methods
- Abstract
- 13.1 Impact of disease on the deposition and disposition of inhaled drugs
- 13.2 Clinical markers (non-imaging) used to investigate small airway disease
- 13.3 Imaging methods: Scintigraphy, SPECT, CT, PET, MRI, CT-CFPD
- 13.4 Lack of meta-analysis – need for standardized approaches to imaging studies and correlation to clinical outcome
- 13.5 Importance of small airways disease and our inability to direct visualize this peripheral zone
- 13.6 Emergence of MRI
- 13.7 Combining HRCT and micro CT
- 13.8 Using imaging to look at pediatric lung disease
- 13.9 Handling errors
- 13.10 Conclusion
- References
- Chapter 14. Machine learning and in silico methods
- Abstract
- 14.1 Introduction
- 14.2 CT imaging-based metrics
- 14.3 Imaging clusters and clinical characteristics
- 14.4 In silico methods and cluster-guided CFPD analysis
- 14.5 From machine and physics-based learning to deep learning
- 14.6 Conclusions
- Acknowledgments
- References
- Chapter 15. The emerging state of the art
- Abstract
- 15.1 Introduction
- 15.2 The potential of in silico aerosol deposition methods and current issues
- 15.3 Synthesis of the emerging state of the art
- References
- Editorial closing remarks
- Index
- No. of pages: 438
- Language: English
- Edition: 1
- Published: January 20, 2021
- Imprint: Academic Press
- Paperback ISBN: 9780128149744
- eBook ISBN: 9780128149751
SK
Stavros Kassinos
Stavros Kassinos is Professor, Computational Sciences Laboratory, University of Cyprus and Computational Science Leader at the University of Cyprus. His research interests center on turbulence and the simulation and modelling of complex physical systems. The overall goal of his research is the understanding of fundamental processes in complex fluid flows and the application of this understanding to the development of new simulation methods in engineering applications. Areas of interest include transport and dispersion in turbulent flows, biological flows with emphasis on inhalation drug delivery, MHD turbulent and laminar flows, and environmental flows. He has been the chair of COST Action MP1404 – “SimInhale”, which has inspired this book. He has served as visiting faculty in the Department of Radiology of the Stanford School of Medicine. Previously, he has worked in the Mechanical Engineering Department at Stanford University as a Postdoctoral Fellow, and as Senior Research Staff at the Stanford/NASA-Ames Center for Turbulence Research (CTR). He held a joint appointment at the Center for Integrated Turbulence Simulations (CITS) at Stanford University. He also holds a Ph.D. from Stanford University.Stavros Kassinos is Professor, Computational Sciences Laboratory, University of Cyprus and Computational Science Leader at the University of Cyprus. His research interests center on turbulence and the simulation and modelling of complex physical systems. The overall goal of his research is the understanding of fundamental processes in complex fluid flows and the application of this understanding to the development of new simulation methods in engineering applications. Areas of interest include transport and dispersion in turbulent flows, biological flows with emphasis on inhalation drug delivery, MHD turbulent and laminar flows, and environmental flows. He has been the chair of COST Action MP1404 – “SimInhale”, which has inspired this book. He has served as visiting faculty in the Department of Radiology of the Stanford School of Medicine. Previously, he has worked in the Mechanical Engineering Department at Stanford University as a Postdoctoral Fellow, and as Senior Research Staff at the Stanford/NASA-Ames Center for Turbulence Research (CTR). He held a joint appointment at the Center for Integrated Turbulence Simulations (CITS) at Stanford University. He also holds a Ph.D. from Stanford University.
Affiliations and expertise
Professor, Computational Sciences Laboratory (UCY-CompSci), Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, CyprusPB
Per Bäckman
Dr Bäckman is senior inhalation consultant at Emmace Consulting AB in Lund Sweden. He is currently focused on the development and application of computer based mechanistic models and in vivo predictive test methods to understand critical product attributes and their influence on the disposition of orally inhaled therapeutics. This includes the impact of dose, aerosol quality and drug dissolution on the rate and extent of drug absorption from the airways. Dr Bäckman holds a PhD from the University of Lund and has been actively engaged in research and development of inhaled therapeutics since 1995. He is also the current co-chair of the Product Quality Research Institute (PQRI) sponsored working group laying the foundation for an inhaled biopharmaceutical classification system.
Affiliations and expertise
Senior Inhalation Consultant, Emmace Consulting AB, Lund, SwedenJC
Joy Conway
Professor Joy Conway is the Professor of Respiratory Sciences, Centre for Health, Medicine and Life Sciences, Brunel University London. Joy has extensive experience as a reseracher and educator with over 25 years in UK Higher Education Institutions. Joy has a strong interest in lung disease, care of those with lung disease, respiratory physiology and pathophysiology and lung imaging. Following qualification as a chartered physiotherapist and a Masters in Rehabilitation (University of Southampton) her PhD (University of Southampton) investigated the use of three-dimensional lung imaging techniques to quantify inhaled aerosol deposition in the lung and structural and functional changes that occur with disease. Joy then progressed through to a personal Chair at the University of Southampton in 2009. In 2019 Joy was appointed as Professor at Brunel University London. At Brunel she is divisional research lead and a Director of the Smart Technologies Advancements for Health and Rehabilitation (STAHR) Research Centre. She is also the national research lead for advancing practice for Health Education England (2019 -) and maintains visiting Professor status with the NIHR Southampton Biomedical Research Centre for Respiratory and Critical Care (2019 -). Joy has extensive expertise in multi-modality, clinical imaging technologies and taking innovations to prototype and patent development. She brings experience in the integration of advanced technologies in healthcare, bridging the academic and health divide. Joy has acted as scientific advisor to several companies.
Affiliations and expertise
Professor, Respiratory Sciences, Centre for Health and Life Sciences, Brunel University, London, UKAH
Anthony J. J. Hickey
Dr. Hickey is Distinguished RTI Fellow, at the Research Triangle Institute and Director of the UNC Catalyst for Rare Diseases of the Eshelman School of Pharmacy He obtained Ph.D. and D.Sc. degrees in pharmaceutical sciences from Aston University, Birmingham, UK. He is a Fellow of the Royal Society of Biology, the American Association of Pharmaceutical Scientists, the American Association for the Advancement of Science and the Royal Society of Medicine. He received the Research Achievement Award of the Particulate Presentations and Design Division of the Powder Technology Society of Japan, the Distinguished Scientist Award of the American Association of Indian Pharmaceutical Scientists; the David W Grant Award in Physical Pharmacy of the American Association of Pharmaceutical Scientists; Thomas T Mercer Joint Prize for Excellence in Inhaled Medicines and Pharmaceutical Aerosols of the American Association for Aerosol Research and the International Society for Aerosols in Medicine and the Ralph Shangraw Memorial Award for Excipient and Excipient Technology of the International Pharmaceutical Excipient Consortium Foundation. He is founder (and formerly President and CEO) of Cirrus Pharmaceuticals, Inc., acquired by Kemwell Pharma; founder (formerly CSO, 2002-2007) of Oriel Therapeutics, Inc, acquired by Sandoz and founder and CEO of Astartein, Inc.; member of the Pharmaceutical Dosage Forms Expert Committee of the United States Pharmacopeia and formerly Chair of the Aerosols Expert Committee of the USP. Dr. Hickey conducts multidisciplinary research programs in the field of pulmonary drug and vaccine delivery for the treatment and prevention of a variety of diseases and oversees research in target and candidate therapeutic agent identification for rare and neglected diseases.
Affiliations and expertise
Distinguished Fellow, Engineered Systems, RTI International, Research Triangle Park, NC, USARead Inhaled Medicines on ScienceDirect